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Method and composition for treating cancer using cellular organelle crystallizing agents

a technology of organelle crystallization and cell, applied in the field of cellular organelle crystallization agents, can solve the problems of no method or agent reported, drug variety, and limited treatment options,

Inactive Publication Date: 2009-04-28
KONG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The present invention provides a new method for treating cancer using a crystallizing agent, such as tetrazolium salt or a substrate of other dehydrogenases. The crystallizing agent sensitizes tumor cells to anticancer therapy, reducing or eliminating the potential for tumor resistance. The method has minimal side effects and is selective in increasing the susceptibility of tumor cells to non-surgical anticancer therapies. The invention also includes a composition comprising a therapeutically effective amount of a crystallizing agent and a therapeutic agent, which may be administered concurrently or sequentially. The composition may also include a pharmaceutically acceptable carrier medium, such as a biocompatible, biodegradable polymer."

Problems solved by technology

However, all of these treatments have been limited by tumor recurrence.
There are no methods or agents that have been reported to choose the centrosome as a target for this purpose.
Unfortunately, a variety of these drugs (such as paclitaxel, docetaxel, etoposide, vincristine, vinblastine, and vinorelbine) are limited by the fact that they all share a common mechanism of action: They bind to tubulin, the molecule of which microtubules are composed, and arrest cells in mitosis by inhibiting spindle assembly (Compton, D. A., et al., (1999) Science 286:313-314).
However, proteins involved in the assembly and the maintenance of the mitotic spindle may be tremendous.
Targeting one specific protein out of this tremendous number of proteins is hardly likely to bring a satisfying inhibition of cell mitosis.
The consequent problem will inevitably be the development of a variety of resistances as seen with other drugs due to the strong regulating ability of the cancer cells.

Method used

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  • Method and composition for treating cancer using cellular organelle crystallizing agents
  • Method and composition for treating cancer using cellular organelle crystallizing agents
  • Method and composition for treating cancer using cellular organelle crystallizing agents

Examples

Experimental program
Comparison scheme
Effect test

example 1

Effect of Crystallizing Agent on 91 Gliosarcoma Tumor Cells

[0068]Tumor cells were exposed to escalating concentrations of SDH substrates, tetrazolium red (TR) and tetrazolium violet (TV), respectively. The tumor cells (4000) were seeded in a 48 well plate one day before treatment was administered. The concentrations of TR and TV were the same, as indicated in FIGS. 1A and 1B, respectively. The concentration was 250, 50, 25, 5, and 0 μg / ml. Tumor cell number was calculated one day post treatment. Surviving tumor cell numbers are shown in FIGS. 1A (treated with TR) and 1B (treated with TV), respectively. These data demonstrate that tetrazolium salts, the substrates of SDH are effective, in a dose dependent manner, in killing tumor cells.

example 2

Synergistic Effect of Crystallizing Agent and Chemotherapeutic Agents on 91 Gliosarcoma

[0069]Crystallizing agents and various chemotherapeutic agents were tested, individually and in combination, on 9 L gliosarcoma tumor cells. Treatment was administered one day after the cells (4000) were seeded in a 48 well plate, with the number of cells counted in 6 hours. MTT at 10 μg / ml was tested with cisplatin and BCNU. MTT at this dose significantly (p<0.005) enhanced the cytotoxic effects of cisplatin (10 μg / ml), and BCNU (25 μg / ml) (FIG. 2). All data represent the mean of 3 to 4 repetitions.

[0070]As is evident from FIG. 2, the crystallizing agent and chemotherapeutic agents are effective in inhibiting tumor cell growth when applied individually. However, the combination of a crystallizing agent and chemotherapeutic agents is demonstrated to be synergistic.

example 3

In Vivo Antitumor Activity of Crystallizing Agent

[0071]Small cell lung Cancer (SCLC) cells (2×105) were injected subcutaneously in rats to test the in vivo cytotoxicity and efficacy of tetrazolium salts. Tetrazolium salts in polylactic acid polymer were implanted in rats with 14 day established 9 L gliosarcoma in the right flank area. Treatment was initiated as follows: G-1, tumor control; G-2, TR in polymer at 2.5 mg / kg; G-3, TV in polymer at 2.5 mg / kg; and G-4, MTT 2.5 mg / kg. The tumor volume was measured on day 60. The tumor size was significantly smaller (p3). See Table 1 and FIG. 3.

[0072]

TABLE 1Group (n)TreatmentTumor size (cm3)P values1 (6)—88.5 ± 23 cm3 2 (6)TR, 2.5 mg / kg44 ± 5.3 cm33 (6)TV, 2.5 mg / kg21 ± 2.3 cm34 (6)MTT, 2.5 mg / kg24 ± 3.6 cm3

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Abstract

This invention provides a method for treating cancer in mammals through cellular-organelle-crystallization-induced-death (herein defined as “Cocid”), a method for treating cancer using cellular organelle and / or cytoskeleton crystallizing agents (e.g. tetrazolium salts and their derivatives), pharmaceutical compositions containing a therapeutically effective amount of organelle and / or cytoskeleton crystallizing agents, and compositions containing organelle and / or cytoskeleton crystallizing agents in combination with a pharmaceutically acceptable carrier, diluent or excipient. The crystallizing agents with or without a pharmaceutically acceptable carrier, diluent or excipient, are used in combination with surgery and / or non-surgical anti-tumor treatments.

Description

CROSS REFERENCE TO RELATED APPLICATION[0001]This application is a continuation-in-part of U.S. patent application Ser. No. 10 / 096,156, filed Mar. 11, 2002 now U.S. Pat. No. 6,864,272, which is a continuation of U.S. patent application Ser. No. 09 / 663,559, now U.S. Pat. No. 6,376,525, filed Sep. 15, 2000, both of which are incorporated herein, in their entirety, by this reference.FIELD OF THE INVENTION[0002]The present invention relates to the use of cellular organelle crystallizing agents to treat cancer cells, to pharmaceutical compositions containing cellular organelle crystallizing agent(s) adapted for such use, and to methods for the treatment of cancer cells by administering cellular organelle crystallizing agent(s).BACKGROUND OF THE INVENTION[0003]Surgery and non-surgical anti-cancer therapies such as radiotherapy, chemotherapy, photodynamic therapy, immunotherapy, electric / chemotherapy, hyperthermia therapy, hyperbaric oxygen therapy, ischemia / reperfusion therapy and gene the...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): A61K31/41A61K31/425C07D257/04C07D257/10C12Q1/26C12Q1/32
CPCA61K31/415A61K31/427A61K31/519A61K31/55A61K31/7048A61K31/7072A61K38/50A61K2300/00
Inventor KONG
Owner KONG
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